Licorice Extract Isoliquiritigenin Protects Endothelial Function in Type 2 Diabetic Mice.

Endothelial dysfunction occurs prior to atherosclerosis, which is an independent predictor of cardiovascular diseases (CVDs). Diabetes mellitus impairs endothelial function by triggering oxidative stress and inflammation in vascular tissues. Isoliquiritigenin (ISL), one of the major bioactive ingredients extracted from licorice, has been reported to inhibit inflammation and oxidative stress.

TRPV2 calcium channel promotes breast cancer progression potential by activating autophagy.

Breast cancer, the most prevalent and aggressive tumor affecting women, requires identification of disease determinants to facilitate the development of effective therapeutic strategies. Transient receptor potential vanilloid 2 (TRPV2), an ion channel highly permeable for calcium (Ca), is implicated in physiological and pathological processes. Nevertheless, the role of TRPV2 in breast cancer remains poorly elucidated.

Asperuloside as a Novel NRF2 Activator to Ameliorate Endothelial Dysfunction in High Fat Diet-Induced Obese Mice.

Current treatments are inadequate in alleviating obesity-associated vascular diseases. The development of effective therapies to ameliorate endothelial dysfunction and attenuate oxidative stress is of utmost importance. Asperuloside (ASP), a bioactive compound extracted from , exhibits antiobesity properties.

IL-4/STAT6 axis observed to reverse proliferative defect in SCA3 patient-derived neural progenitor cells.

Spinocerebellar ataxia 3 (SCA3) is an incurable, neurodegenerative genetic disorder that leads to progressive cerebellar ataxia and other parkinsonian-like pathologies because of loss of cerebellar neurons. The role of an expanded polyglutamine aggregate on neural progenitor cells is unknown. Here, we show that SCA3 patient-specific induced neural progenitor cells (iNPCs) exhibit proliferative defects.

Type 2 cytokines promote angiogenesis in ischemic muscle via endothelial IL-4Rα signaling.

Peripheral arterial disease (PAD) is one of the leading causes of cardiovascular morbidity and mortality worldwide, yet current trials on therapeutic angiogenesis remain suboptimal. Type 2 immunity is critical for post-ischemic regeneration, but its regulatory role in revascularization is poorly characterized. Here, we show that type 2 cytokines, interleukin-4 (IL-4) and interleukin-13 (IL-13), are the key mediators in post-ischemic angiogenesis.

Physiological concentration of protocatechuic acid directly protects vascular endothelial function against inflammation in diabetes through Akt/eNOS pathway.

Background: Cardiovascular diseases (CVDs) have been the major cause of mortality in type 2 diabetes. However, new approaches are still warranted since current diabetic medications, which focus mainly on glycemic control, do not effectively lower cardiovascular mortality rate in diabetic patients. Protocatechuic acid (PCA) is a phenolic acid widely distributed in garlic, onion, cauliflower and other plant-based foods.

Association between immune checkpoint inhibitors and myocardial infarction in Asians: A population-based self-controlled case series.

Background: While immune checkpoint inhibitors (ICIs) are associated with elevated cardiovascular risks, evidence of any association between ICIs and myocardial infarction (MI) was scarce, especially in Asians.

Methods: Using prospectively collected population-based data, this self-controlled case series included patients prescribed an ICI between 1/1/2014 and 31/12/2020 in Hong Kong who had MI within January 1, 2013 to December 31, 2021. Incidence rate ratios (IRRs) for MI during and after ICI exposure were estimated, compared to the year before ICI initiation.

Association Between Visit-to-Visit Lipid Variability and Incident Cancer: A Population-based Cohort Study.

Dyslipidemia is associated with increased cancer risk. However, the prognostic value of visit-to-visit lipid variability (VVLV) is unexplored in this regard. To investigate the associations between the VVLV and the risk of incident cancer, we conducted a retrospective cohort study on adult patients attending a family medicine clinic in Hong Kong during 2000-2003, excluding those with <3 tests for low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and total cholesterol (TC) each, those with prior cancer diagnosis, and those with <1 year of follow-up.

Cardiovascular Outcomes and Hospitalizations in Asian Patients Receiving Immune Checkpoint Inhibitors: A Population-based Study.

Immune checkpoint inhibitors (ICI) have known associations with cardiotoxicity. However, a representative quantification of the adverse cardiovascular events and cardiovascular attendances amongst Asian users of ICI has been lacking. This retrospective cohort study identified all ICI users in Hong Kong, China, between 2013 and 2021.

Type 2 innate immunity drives distinct neonatal immune profile conducive for heart regeneration.

Neonatal immunity is functionally immature and skewed towards a T2-driven, anti-inflammatory profile. This neonatal immunotolerance is partly driven by the type 2 cytokines: interleukin-4 (IL-4) and interleukin-13 (IL-13). Studies on neonatal cardiac regeneration reveal the beneficial role of an anti-inflammatory response in restoring cardiac function after injury.

Butyrate protects endothelial function through PPARδ/miR-181b signaling.

Reports of the beneficial roles of butyrate in cardiovascular diseases, such as atherosclerosis and ischemic stroke, are becoming increasingly abundant. However, the mechanisms of its bioactivities remain largely unknown. In this study, we explored the effects of butyrate on endothelial dysfunction and its potential underlying mechanism.

Potential of crocodile blood as a medication and dietary supplement: A systemic review.

Crocodile blood has long been used as a traditional medicine in many Asian countries to treat diseases such as asthma, allergies, and many others. Yet, only recently has the safety and effectiveness of using crocodile blood as a medicine been examined using modern scientific methods; with both conserved and novel active components identified from crocodile blood. Further in vitro and in vivo investigations found that crocodile blood can have a wide range of beneficial effects, including antimicrobial, antiviral, anti-oxidative, anti-inflammatory, antitumour effects, anti-anaemia, and enhancement of wound healing.

Chronic black tea extract consumption improves endothelial function in ovariectomized rats.

Purpose: Menopause escalates the risk of cardiovascular diseases in women. There is an unmet need for better treatment strategy for estrogen-deficiency-related cardiovascular complications. Here we investigated the impact of chronic black tea extract (BT) consumption on cardiovascular function and lipid metabolism using a rat model of estrogen deficiency.

Regulation of multiple transcription factors by reactive oxygen species and effects of pro-inflammatory cytokines released during myocardial infarction on cardiac differentiation of embryonic stem cells.

Background: The mechanism of how reactive oxygen species (ROS) regulate cardiac differentiation in the long-run is unclear and the effect of pro-inflammatory cytokines secreted during myocardial infarction on the cardiac differentiation of embryonic stem cells (ESCs) is unknown. The aims of this study were 1) to investigate the effect of ROS on cardiac differentiation and the regulations of transcription factors in ESC differentiation cultures and 2) to investigate the effect of pro-inflammatory cytokines on the expression of cardiac structural genes and whether this effect is mediated through ROS signaling.

Methods: ESCs were differentiated using hanging drop method.

Chronic cranberry juice consumption restores cholesterol profiles and improves endothelial function in ovariectomized rats.

Purpose: Postmenopausal women experience higher risks for cardiovascular diseases than age-matched men and pre-menopausal women. There is a need for better treatment strategy for estrogen-deficient-related cardiovascular complications. We and others have recently reported that activated renin-angiotensin system and the associated oxidative stress impaired endothelium-dependent relaxation in ovariectomized rat, while angiotensin receptor blocker rescues endothelial dysfunction.

Catalysis-based inhibitors of the calcium signaling function of CD38.

CD38 is a signaling enzyme responsible for catalyzing the synthesis of cyclic ADP ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate; both are universal Ca(2+) messenger molecules. Ablation of the CD38 gene in mice causes multiple physiological defects, including impaired oxytocin release, that result in altered social behavior. A series of catalysis-based inhibitors of CD38 were designed and synthesized, starting with arabinosyl-2'-fluoro-2'-deoxynicotinamide mononucleotide.

Bone morphogenic protein-4 induces endothelial cell apoptosis through oxidative stress-dependent p38MAPK and JNK pathway.

The expression of bone morphogenic protein 4 (BMP4), a new pro-inflammatory marker, is increased by disturbed flow in endothelial cells (ECs). BMP4 stimulates production of reactive oxygen species (ROS) and causes endothelial cell dysfunction. The present study examined BMP4-induced apoptosis in ECs and isolated arteries from rat, mouse, and human, and the signaling pathways mediating BMP4-induced apoptosis.

Raloxifene improves vascular reactivity in pressurized septal coronary arteries of ovariectomized hamsters fed cholesterol diet.

Although vascular effects of selective estrogen receptor modulators (SERMs) have been extensively examined in conduit arteries, whether SERMs could favorably modulate myogenic response in resistance arteries is unknown. The impact of raloxifene therapy and cholesterol diet on myogenic constriction during estrogen deficiency is unresolved. This study investigated changes in vascular reactivity and myogenic responses in female ovariectomized (Ovx) hamsters fed high-cholesterol diet (HCD) with and without chronic treatment of raloxifene.

Oxidative stress-dependent cyclooxygenase-2-derived prostaglandin f(2α) impairs endothelial function in renovascular hypertensive rats.

Unlabelled: Abstract Aims: The role of endothelium-derived contracting factors (EDCFs) in regulating renovascular function is yet to be elucidated in renovascular hypertension (RH). The current study investigated whether oxidative stress-dependent cyclooxygenase (COX)-2-derived prostaglandin F(2α) (PGF(2α)) impairs endothelial function in renal arteries of renovascular hypertensive rats (RHR).

Results: Renal hypertension was induced in rats by renal artery stenosis of both kidneys using the 2-kidney 2-clip model.

Inhibition of renin-angiotensin system reverses endothelial dysfunction and oxidative stress in estrogen deficient rats.

Background: Estrogen deficiency increases the cardiovascular risks in postmenopausal women. Inhibition of the renin-angiotensin system (RAS) and associated oxidative stress confers a cardiovascular protection, but the role of RAS in estrogen deficiency-related vascular dysfunction is unclear. The present study investigates whether the up-regulation of RAS and associated oxidative stress contributes to the development of endothelial dysfunction during estrogen deficiency in ovariectomized (OVX) rats.

Design, synthesis and biological characterization of novel inhibitors of CD38.

Human CD38 is a novel multi-functional protein that acts not only as an antigen for B-lymphocyte activation, but also as an enzyme catalyzing the synthesis of a Ca(2+) messenger molecule, cyclic ADP-ribose, from NAD(+). It is well established that this novel Ca(2+) signaling enzyme is responsible for regulating a wide range of physiological functions. Based on the crystal structure of the CD38/NAD(+) complex, we synthesized a series of simplified N-substituted nicotinamide derivatives (Compound 1-14).

Bone morphogenic protein-4 impairs endothelial function through oxidative stress-dependent cyclooxygenase-2 upregulation: implications on hypertension.

Rationale: Bone morphogenic protein (BMP)4 can stimulate superoxide production and exert proinflammatory effects on the endothelium. The underlying mechanisms of how BMP4 mediates endothelial dysfunction and hypertension remain elusive.

Objective: To elucidate the cellular pathways by which BMP4-induced endothelial dysfunction is mediated through oxidative stress-dependent upregulation of cyclooxygenase (COX)-2.

Therapeutically relevant concentrations of raloxifene dilate pressurized rat resistance arteries via calcium-dependent endothelial nitric oxide synthase activation.

Objective: Selective estrogen receptor modulators (SERMs) inhibit constriction of mammalian conduit arteries. However, it is unknown whether SERMs at therapeutically achievable concentrations could reduce vascular tone in resistance arteries. The present study aimed to examine roles of Ca(2+) influx in endothelium and endothelial nitric oxide synthase (eNOS) activation in dilatations induced by raloxifene, a second-generation SERM in myogenically active arteries.

Cyclic guanosine monophosphate dependent pathway contributes to human mast cell inhibitory actions of the nitric oxide donor, diethylamine NONOate.

We have previously demonstrated that exogenous nitric oxide (NO) inhibited anti-IgE-mediated histamine release from human cultured mast cells. In the current study, we further investigated if syntheses of eicosanoids and cytokines were also suppressed by NO donors and evaluated if activation of soluble guanylyl cyclase (sGC) was an underlying mechanism. The effects of the NO donor diethylamine NONOate (DEA/NO) on IgE-dependent syntheses of eicosanoids (prostaglandin D(2) and cysteinyl leukotrienes) and cytokines (tumor necrosis factor-alpha and interleukin-8) from buffy coat derived human cultured mast cells were examined.